We shall study interrelationships among human growth hormone, Factor VIII, diabetes mellitus and macrovascular disease. Human growth hormone will be studied as a family of proteins. Modification of the intact 191 amino acid, single chain "prohormone" results in activation with formation of 2-chain derivatives, some of which are diabetogenic. Structure function studies of the cleaved forms will be made by devising radioimmunoassays and receptor assays for their measurement in plasma, in relation to sleep, and to glucose and suppressing drugs, with particular emphasis on the in vivo and in vitro effects of hGH on the formation of the multiple forms of Factor VIII. The forms of hGH and of Factor VIII will be related to diabetes in 18 to 35 year old patients and controls, in acromegaly and in hypopituitary short stature patients receiving hGH and its modifications. In diabetic patients, studies will be made of the popliteal arteries, blood flow in the legs, echocardiography, retinal state and these will be correlated with the biochemical findings. The umbilical cords of normal and diabetic mothers will be used to culture endothelial cells and they will be studied for Factor VIII production in response to stimulation with specific hGH derivatives.